Clinical characteristics
During the 6-month study period, a total of 547 cases of S. aureus (260, 141, 141, 20, and 101 cases of MRSA, A. baumannii [MRAB, n=87], P. aeruginosa [MRPA, n=18], CRE, and VRE bacteraemia, respectively) occurred in the 10 hospitals. The flows of case and control selection are shown in Figure 1.
The rate of infection acquired while in an intensive care unit was lowest for MRSA (16.5%) and highest for MRAB (58.6%) bacteraemia. Although the median LOS was longest for CRE (53 days) the median post-bacteraemia LOS was longest for MRPA (33 days). The in-hospital mortality rates, highest for CRE (65.0%), were 62.1% and 49.5% for MRAB and VRE bacteraemia, respectively, and lowest for MRPA (16.7%) and MRSA (28.1%) bacteraemia. The 90-day mortality rate was higher in MDRO than in susceptible bacteraemia patients for S. aureus and A. baumannii infection. Baseline characteristics and clinical outcomes are shown in Table 1. See web-only Supplementary Tables S1 and S2 for the mortality rates by age groups. Survival curves are shown in Figure 2.
Table 1
Clinical characteristics and outcomes of enrolled patients with bacteraemia due to multidrug-resistant organisms for six-month period from ten hospitals in Korea
| S. aureus | A. baumannii | P. aeruginosa | Enterobacteriaceae | Enterococcus |
| MRSA n=260 | MSSA n=287 | p-value | MRAB n=87 | Non-MDR ABA n=54 | p-value | MRPA n=18 | Non-MDR PAE n=123 | p-value | CRE N=20 | VRE N=101 |
Age (years) | 65.7 (21.2) | 62.0 (21.8) | 0.044 | 64.9 (18.2) | 54.1 (18.1) | 0.784 | 68.8 (14.7) | 67.1 (14.4) | 0.640 | 69.8 (15.8) | 66.9 (14.2) |
Sex (male) | 156 (60.6%) | 165 (57.5%) | 0.552 | 55 (63.2%) | 32 (59.3%) | 0.638 | 11 (61.1%) | 78 (63.4%) | 0.850 | 9 (45.0%) | 57 (56.4%) |
Location | | | | | | | | | | | |
| Ward | 98 (37.7%) | 99 (34.5%) | 0.005 | 22 (25.3%) | 32 (59.3%) | <0.001 | 7 (38.9%) | 63 (51.2%) | 0.018 | 10 (50.0%) | 65 (64.4%) |
Intensive care unit | 43 (16.5%) | 23 (8.0%) | 51 (58.6%) | 9 (16.7%) | 8 (44.4%) | 20 (16.3%) | 9 (45.0%) | 27 (26.7%) |
Emergency room | 119 (45.8%) | 164 (57.1%) | 14 (16.1%) | 12 (22.2%) | 3 (16.7%) | 40 (32.5%) | 1 (5.0%) | 9 (8.9%) |
Out-patient clinic | 0 | 1 (0.3%) | 0 | 1 (1.9%) | 0 | 0 | 0 | 0 |
Length of stay (median, (IQR)) | 28 (12-51) | 19 (10-35) | 0.001 | 27 (13-52) | 19 (9-41) | 0.101 | 40 (28-90) | 19 (10-36) | <0.001 | 53 (22-95) | 43 (26-75) |
Post bacteraemia LOS (median, (IQR)) | 17 (7-38) | 16 (8-29) | 0.255 | 7 (1-22) | 11 (7-20) | 0.166 | 33 (19-61) | 11 (4-21) | <0.001 | 27 (9-32) | 25 (12-68) |
SOFA score (median, (IQR)) | 4 (1-8) | 3 (1-6) | 0.003 | 8 (5-13) | 3 (1-7) | <0.001 | 5 (3-8) | 4 (2-6) | 0.408 | 7 (4-13) | 4 (2-6) |
Mortality | | | | | | | | | | | |
| In hospital | 73 (28.1%) | 57 (19.9%) | 0.024 | 54 (62.1%) | 13 (24.1%) | <0.001 | 3 (16.7%) | 32 (26.0%) | 0.391 | 13 (65.0%) | 50 (49.5%) |
7 days | 30 (11.5%) | 26 (9.1%0 | 0.628 | 40 (46.0%) | 9 (16.7%) | 0.001 | 1 (5.6%) | 19 (15.4%) | 0.369 | 5 (25.0%) | 18 (17.9%) |
30 days | 68 (26.2%) | 52 (18.1%) | 0.023 | 49 (56.3%) | 12 (22.2%) | <0.001 | 1 (5.6%) | 29 (23.6%) | 0.069 | 9 (45.0%) | 40 (39.6%) |
90 days | 79 (30.4%) | 57 (19.9%) | 0.017 | 55 (63.2%) | 13 (24.1%) | <0.001 | 3 (16.7%) | 40 (32.5%) | 0.368 | 11 (55.0%) | 48 (47.5%) |
Note. MRSA; methicillin resistant S. aureus, MSSA; methicillin susceptible S. aureus, MRAB; multidrug resistant A. baumannii, MDR; multidrug resistant, ABA; A. baumannii, MRPA; multidrug resistant P. aeruginosa, PAE; P. aeruginosa, CRE; carbapenem resistant Enterobacteriaceae, VRE; vancomycin resistant Enterococcus, LOS; length of stay, SOFA; Sequential Organ Failure Assessment |
Additional hospital costs and LOS, MDRO versus infection with susceptible organisms
As shown in Table 2, the mean LOS difference was 1.0 day between the R-group and S-group, and the mean difference in hospital cost was $1,089 for S. aureus bacteraemia; these were longest and highest in the R-group for Enterobacteriaceae, respectively. Compared to the S-group, R-group cases caused 2.3 additional days of hospital stay and $7,507 additional hospital costs for A. baumannii bacteraemia.
Table 2
Differences in costs and lengths of hospital stay between patients with multidrug-resistant and corresponding susceptible organisms’ bacteraemia
Organisms | S. aureus | A. baumannii | P. aeruginosa | Enterobacteriaceae | Enterococcus |
Group | MRSA (n=163) | MSSA (n=163) | MRAB (n=27) | Non-MDR ABA (n=27) | MRPA (n=13) | Non-MDR PAE (n=13) | CRE (n=13) | Susceptible Enterobact- eriaceae (n=13) | VRE (n=72) | Susceptible Enterococcus (n=27) |
LOS (d) | 29.8 (± 30.2) | 28.8 (± 31.1) | 30.2 (± 29.1) | 27.9 (± 24.0) | 41.6 (± 20.9) | 27.3 (± 28.6) | 55.4 (± 43.8) | 21.3 (± 14.0) | 48.2 (± 35.1) | 41.3 (± 29.3) |
LOS difference (d) | 1.0 (± 38.1) | 2.3 (± 26.8) | 14.3 (± 28.1) | 34.1 (± 48.2) | 6.8 (± 47.9) |
Hospital cost ($) | 16,386 (±17,320) | 15,297 (± 16,820) | 24,452 (± 24,918) | 16,946 (± 16,515) | 26,168 (± 14,944) | 17,447 (± 14,320) | 73,248 (± 63,761) | 14,998 (± 15,053) | 47,779 (± 47,430) | 33,365 (± 35,850) |
Hospital cost difference ($) | 1,089 (± 23,240) | 7,507 (± 16,110) | 8,721 (± 16,304) | 58,250 (± 68,426) | 14414 (± 57934) |
Note. MRSA; methicillin resistant S. aureus, MSSA; methicillin susceptible S. aureus, MRAB; multidrug resistant A. baumannii, MDR; multidrug resistant, ABA; A. baumannii, MRPA; multidrug resistant P. aeruginosa, PAE; P. aeruginosa, CRE; carbapenem resistant Enterobacteriaceae, VRE; vancomycin resistant Enterococcus, LOS; length of stay |
Additional Hospital Costs And Los, Mdro Versus No Infection
As shown in Table 3, the mean LOS difference between the R-group and N-group was 24 days, and the mean difference in hospital cost was $15,768 for S. aureus bacteraemia; these were longest and highest in the R-group for Enterobacteriaceae, respectively. Compared to the N-group, the R-group was associated with 24 additional days of hospital stay and $35,682 additional hospital costs for A. baumannii bacteraemia.
Table 3
Differences in costs and length of hospital stay differences between patients with multidrug resistant organisms’ bacteraemia and no infection
Organisms | S. aureus | A. baumannii | P. aeruginosa | Enterobacteriaceae | Enterococcus |
Group | MRSA (n=113) | Non-infection control (n=113) | MRAB (n=56) | Non-infection control (n=56) | MRPA (n=5) | Non-infection control (n=5) | CRE (n=9) | Non-infection control (n=9) | VRE (n=74) | Non-infection control (n=74) |
LOS (d) | 43.1 (± 34.7) | 18.9 (± 14.7) | 39.3 (± 35.9) | 15.3 (± 16.6) | 56.2 (± 29.1) | 14.4 (± 5.7) | 69.6 (± 44.5) | 19.0 (± 14.2) | 46.4 (± 34.2) | 18.8 (± 14.7) |
LOS difference (d) | 24.2 (± 33.8) | 24.4 (± 38.1) | 41.8 (± 30.9) | 50.5 (± 41.9) | 27.2 (± 34.7) |
Hospital cost ($) | 26,508 (± 29,197) | 10,740 (± 10,017) | 46,178 (± 39,208) | 10,570 (± 9,788) | 49,335 (± 45,871) | 9,426 (± 4,689) | 86,082 (± 62,469) | 14,031 (± 12,571) | 45,334 (± 45,809) | 11,616 (± 11,670) |
Hospital cost difference ($) | 15,768 (± 27,877) | 35,682 (± 35,082) | 39,908 (± 41,840) | 72,051 (± 58,489) | 33,662 (± 42,144) |
Note. MRSA; methicillin resistant S. aureus, MRAB; multidrug resistant A. baumannii, MRPA; multidrug resistant P. aeruginosa, CRE; carbapenem resistant Enterobacteriaceae, VRE; vancomycin resistant Enterococcus, LOS; length of stay |
Cost of caregiver and productivity loss due to unexpected death
The additional cost of caregiving in the R-group due to extended LOS compared to the N-group was $1,405 for S. aureus and A. baumannii; $2,401 for P. aeruginosa; $2,928 for Enterobacteriaceae; and $1,581 for Enterococcus bacteraemia.
The estimated number of deaths that occurred nationwide was 3,280 cases, which included 1,237, 882, 36, 254, and 871 for MRSA, MRAB, MRPA, CRE, and VRE bacteraemia, respectively. See web-only Supplementary Tables S1 and S2 for the estimated number of deaths per age group. The estimated productivity loss due to unexpected death was $14,811,599; $22,613,346; $1,121,030; $11,284,929; and $14,579,883 for MRSA, MRAB, MRPA, CRE, and VRE bacteraemia, respectively.
Total Burden Of Mdro Infection And Sensitivity Analyses
The total socioeconomic burden of MDRO infection, estimated as the total additional medical cost, cost of hiring a caregiver, and the sum of productivity loss due to unexpected death, was $294,505,002 (Table 4). In sensitivity analyses, in the standard model (Model 1), the economic burden was $81,847,359; $73,406,391; $10,082,672; $45,175,327; and $77,765,842 for MRSA, MRAB, MRPA, CRE, and VRE bacteraemia, respectively, with a total burden of MDRO bacteraemia of $288,277,591. The total burden of MDRO bacteraemia ranged from $170,627,020 to $416,094,679. The economic burden on both ends of the limit is shown in Table 5.
Table 4
Results of socioeconomic burden estimation of five multidrug-resistant organisms’ bacteraemia
Values | MRSA | MRAB | MRPA | CRE | VRE |
Number of cases in 2017 (N) | 4,070 | 1,396 | 218 | 461 | 1,834 |
Hospital cost differences (C) ($) | 15,768 | 35,682 | 39,908 | 72,051 | 33,662 |
LOS differences (L) (d) | 24 | 24 | 41 | 50 | 27 |
90 days mortality rate | 30.4% | 63.2% | 16.7% | 55.0% | 47.5% |
Total hospital cost (NXC) ($) | 64,175,760 | 49,812,072 | 8,699,944 | 33,215,511 | 61,736,108 |
Excess Cost of caregiver use* ($) (L X 65,000/1110) | 1405.4 | 1405.4 | 2400.9 | 2927.9 | 1581.1 |
Total cost of excess caregiver use ($) (LX65000/1110XN) | 5,720,000 | 1,961,946 | 523,396 | 1,349,775 | 2,899,703 |
Estimated Number of deaths in 1 year | 1,237 | 882 | 36 | 254 | 871 |
Productivity loss due to mortality* ($) | 14,811,599 | 22,613,346 | 1,121,030 | 11,284,929 | 14,579,883 |
Total socioeconomic burden ($) | 84,707,359 | 74,387,364 | 10,344,370 | 45,850,215 | 79,215,694 |
Sum of the socioeconomic burden of MDROs ($) | 294,505,002 |
Note. MRSA; methicillin resistant S. aureus, MRAB; multidrug resistant A. baumannii, MRPA; multidrug resistant P. aeruginosa, CRE; carbapenem resistant Enterobacteriaceae, VRE; vancomycin resistant Enterococcus * caregiver hire rate: 100% * annual discount rate: 5%, employment rate of patients 25% |
Table 5
Sensitivity analyses for socioeconomic burden estimation of five multidrug-resistant organisms’ bacteraemia
Values | MRSA | MRAB | MRPA | CRE | VRE |
Model 1; Standard model. Hire of caregiver: 50%, annual discount rate 5%, employment rate of patients 25% | | |
| Mean hospital cost differences ($) | 15,768 | 35,682 | 39,908 | 72,051 | 33,662 |
Total additional hospital cost ($) | 64,175,760 | 49,812,072 | 8,699,944 | 33,215,511 | 61,736,108 |
Total cost of excess caregiver use ($) | 2,860,000 | 980,973 | 261,698 | 674,887 | 1,449,851 |
Productivity loss due to mortality ($) | 14,811,599 | 22,613,346 | 1,121,030 | 11,284,929 | 14,579,883 |
Total socioeconomic burden ($) | 81,847,359 | 73,406,391 | 10,082,672 | 45,175,327 | 77,765,842 |
Model 2; lower end model. Hire of caregiver: 25%, annual discount rate 7%, employment rate of patients 15% | | |
| 95% lower limit of mean hospital cost differences (C) ($) | 10,572 | 26,287 | -12,043 | 27,,093 | 23,898 |
Total additional hospital cost ($) | 43,028,040 | 36,696,652 | -2,625,374 | 12,489,873 | 43,828,932 |
Total cost of excess caregiver use ($) | 1,430,000 | 490,486 | 130,849 | 337,443 | 724,926 |
Productivity loss due to mortality ($) | 7,989,640 | 11,942,500 | 556,942 | 5,845,378 | 7,760,733 |
Total socioeconomic burden ($) | 52,447,680 | 49,129,638 | -1,937,583 | 18,672,694 | 52,314,591 |
Model3; upper end model. Hire of caregiver: 75%, annual discount rate 3%, employment rate of patients 35% | | |
| 95% upper limit of mean hospital cost differences (C) ($) | 20,964 | 45,077 | 91,860 | 117,010 | 43,426 |
Total additional hospital cost ($) | 85,323,480 | 62,927,492 | 20,025,480 | 53,941,610 | 79,643,284 |
Total cost of excess caregiver use ($) | 4,290,000 | 1,471,459 | 392,547 | 1,012,331 | 2,174,777 |
Productivity loss due to mortality ($) | 23,399,641 | 37,080,110 | 1,947,344 | 23,745,907 | 18,719,216 |
Total socioeconomic burden ($) | 113,013,121 | 101,479,061 | 22,365,371 | 78,699,848 | 100,537,277 |
Note. MRSA; methicillin resistant S. aureus, MRAB; multidrug resistant A. baumannii, MRPA; multidrug resistant P. aeruginosa, CRE; carbapenem resistant Enterobacteriaceae, VRE; vancomycin resistant Enterococcus |